Heat stroke is a medical emergency that has become more prevalent in recent years due to the increased popularity of "fun runs." The pathophysiology of this disorder remains obscure, but the preeminent role of the cardiovascular system is certainly recognized. At a recent international workshop on the subject it was recommended that animal models be developed to specifically investigate blood flow distribution to the liver, kidney, skin, and CNS during hyperthermia. This proposal addresses that need directly. Using the chloralose anesthetized rat as an animal model, we have preliminary evidence indicating that a selective loss of splanchnic vascular control may be the fatal mechanism leading to circulatory failure in hyperthermia. We hypothesize that this is indeed the case and that the impairment is mediated in part by the release of endogenous opioids that interact with ongoing autonomic activity. We propose to (a) determine the sequence and nature of the cardiac and peripheral vascular responses to the prodromal period of heat stroke; (b) correlate the changes in blood chemistry with cardiovascular events and histological damage; (c) determine the effects of adrenalectomy and splanchnic sympathectomy on the peripheral vascular response to hyperthermia; (d) monitor splanchnic sympathetic nerve activity to heat stress; (e) determine if an elevated brain temperature potentiates cardiovascular insufficiency; (f) determine the effects of naloxone on survival and circulatory stability; and (g) determine if animals that survive a hyperthermic episode sustain brain lesions, and if so, do these animals manifest impaired thermoregulatory function. Measurements will include renal, superior mesenteric, and caudal blood flows, cardiac output, mean arterial pressure, and hypothalamic, core, and mean skin temperatures. In specific protocols, we will also measure sympathetic nerve activity and blood catecholamines (NE,DA,E), pH, Na+, K+, lactate, and endotoxin. The significance of this research lies in its contribution to understanding basic physiological mechanisms underlying heat stroke and other shock syndromes. It may also provide evidence to support alternative means of treating heat stroke victims.